Plasma Quercetin Levels Research Articles

Combination of α-Glycosyl-Isoquercitrin and Soybean Fiber Promotes Quercetin Bioavailability and Glucagon-like Peptide-1 Secretion and Improves Glucose Homeostasis in Rats Fed a High-Fat High-Sucrose Diet.

This study examined the effects of a combination of soybean fiber and α-glycosyl-isoquercitrin (AGIQ) on improving quercetin bioavailability and glucose metabolism in rats fed an obesogenic diet. For 9 weeks, rats were individually fed a control diet, a high-fat high-sucrose (H) diet, H with soybean fiber (HS), or with AGIQ (HQ), or with both (HSQ). Quercetin derivatives in plasma, feces, urine, and cecal content were quantified by high-performance liquid chromatography to assess the bioavailability of quercetin, and meal tolerance tests were performed to assess postprandial glycemia and glucagon-like peptide-1 (GLP-1) responses. The HSQ group had higher plasma quercetin levels than HQ. The postprandial glycemia was attenuated in the HSQ group when compared to the H group. The basal plasma GLP-1 concentrations positively correlated with plasma quercetin derivative concentrations. Hence, the combination of soybean fiber and AGIQ could be beneficial for reducing the risk of glucose intolerance, possibly involving enhanced quercetin bioavailability and GLP-1 secretion.

Quercetin and Green Tea Extract Supplementation Downregulates Genes Related to Tissue Inflammatory Responses to a 12-Week High Fat-Diet in Mice.

Quercetin (Q) and green tea extract (E) are reported to counter insulin resistance and inflammation and favorably alter fat metabolism. We investigated whether a mixture of E + Q (EQ) could synergistically influence metabolic and inflammation endpoints in a high-fat diet (HFD) fed to mice. Male C57BL/6 mice (n = 40) were put on HFD (fat = 60%kcal) for 12 weeks and randomly assigned to Q (25 mg/kg of body weight (BW)/day), E (3 mg of epigallocatechin gallate/kg BW/day), EQ, or control groups for four weeks. At 16 weeks, insulin sensitivity was measured via the glucose tolerance test (GTT), followed by area-under-the-curve (AUC) estimations. Plasma cytokines and quercetin were also measured, along with whole genome transcriptome analysis and real-time polymerase chain reaction (qPCR) on adipose, liver, and skeletal muscle tissues. Univariate analyses were conducted via analysis of variance (ANOVA), and whole-genome expression profiles were examined via gene set enrichment. At 16 weeks, plasma quercetin levels were higher in Q and EQ groups vs. the control and E groups (p < 0.05). Plasma cytokines were similar among groups (p > 0.05). AUC estimations for GTT was 14% lower for Q vs. E (p = 0.0311), but non-significant from control (p = 0.0809). Genes for cholesterol metabolism and immune and inflammatory response were downregulated in Q and EQ groups vs. control in adipose tissue and soleus muscle tissue. These data support an anti-inflammatory role for Q and EQ, a result best captured when measured with tissue gene downregulation in comparison to changes in plasma cytokine levels.

Higher plasma quercetin levels following oral administration of an onion skin extract compared with pure quercetin dihydrate in humans.

To investigate the plasma kinetics of quercetin derived from hard capsules filled with onion skin extract powder or quercetin dihydrate in humans. In a randomized, single-blind, diet-controlled crossover study, 12 healthy subjects (six men and six women) aged 21-33years were administered a single oral supra-nutritional dose of approximately 163mg quercetin derived from onion skin extract powder (containing 95.3% of total flavonoids as quercetin aglycone) or quercetin dihydrate (134mg quercetin aglycone equivalent). Blood samples were collected before and during a 24-h period after quercetin administration. The concentrations of quercetin and its two monomethylated derivatives, isorhamnetin (3'-O-methyl quercetin), and tamarixetin (4'-O-methyl quercetin), were measured using HPLC with fluorescence detection after plasma enzymatic treatment. The systemic availability, determined by comparing the plasma concentration-time curves of quercetin, was 4.8 times higher, and the maximum plasma concentration (C max) was 5.4 times higher after ingestion of the onion skin extract than after ingestion of pure quercetin dihydrate. By contrast, t max did not differ significantly between the two formulations. The C max values for isorhamnetin and tamarixetin were 3.8 and 4.4 times higher, respectively, after administration of onion skin extract than after pure quercetin dihydrate. The plasma kinetics of quercetin were not significantly different in men and women. Quercetin aglycone derived from onion skin extract powder is significantly more bioavailable than that from quercetin dihydrate powder filled hard capsules.

The effects of quercetin supplementation on cognitive functioning in a community sample: a randomized, placebo-controlled trial

The purpose of the present study was to examine the effects of quercetin supplementation on neurocognitive functioning. A large community sample (n = 941) completed a 12-week supplementation protocol, and participants were randomly assigned to receive 500 mg/day or 1000 mg/day quercetin, or placebo. Results failed to indicate significant effects of quercetin on memory, psychomotor speed, reaction time, attention, or cognitive flexibility, despite large increases in plasma quercetin levels among the quercetin treatment groups. Consistent with recent research, this study raises concerns regarding the generalizability of positive findings of in vitro and animal quercetin research, and provides evidence that quercetin may not have an ergogenic effect on neurocognitive functioning in humans.

The Acute Effect of Ingesting a Quercetin-Based Supplement on Exercise-Induced Inflammation and Immune Changes in Runners

This study tested the acute anti-inflammatory and immune-modulating influence of a quercetin-based supplement consumed by endurance athletes 15 min before an intense 2-hr run. In this randomized, crossover study, 20 runners (11 men, 9 women, age 38.4 ± 2.1 yr) completed two 2-hr treadmill runs at 70% VO(2max) (3 wk apart). Subjects ingested either 4 quercetin-based chews (Q-chew) or placebo chews (PL) 15 min before the runs. The 4 Q-chews provided 1,000 mg quercetin, 120 mg epigallocatechin 3-gallate, 400 mg isoquercetin, 400 mg each eicosapentaenoic acid and docosahexaenoic acid, 1,000 mg vitamin C, and 40 mg niacinamide. Subjects provided blood samples 30 min before, immediately after, and 1 hr postexercise and were analyzed for plasma quercetin, total blood leukocytes (WBC), C-reactive protein (CRP), 9 cytokines (IL-6, TNFα, GM-CSF, IFNγ, IL-1β, IL-2, IL-8, IL-10, and IL-12p70), granulocyte (GR) and monocyte (MO) phagocytosis (PHAG), and oxidative-burst activity (OBA). Plasma quercetin increased from 80.0 ± 26.0 μg/L to 6,337 ± 414 μg/L immediately postexercise and 4,324 ± 310 μg/L 1 hr postexercise after ingestion of Q-chews, compared with no change in PL (p < .001). Exercise caused significant increases in, CRP, GM-CSF, IL-10, IL-1β, IL-2, IL-6, IL-8, TNFα, GR-PHAG, and MO-PHAG and decreases in GR-OBA and MO-OBA, but no differences in the pattern of change were measured between Q-chew and PL trials. Acute ingestion of Q-chews 15 min before heavy exertion caused a strong increase in plasma quercetin levels but did not counter postexercise inflammation or immune changes relative to placebo.

The Acute Effect of Ingesting a Quercetin-Based Supplement On Exercise-Induced Inflammation In Runners

PURPOSE: This study tested the acute anti-inflammatory influence of a quercetin-based supplement consumed by endurance athletes 15-min prior to an intense 2-h run. Design: In this randomized, crossover study, 20 long distance runners (N=11 males, N=9 females, age 38.4±2.1 y, VO2max 52.6±2.0) completed two 2-h treadmill runs at 70% VO2max (3 weeks apart) that incorporated a closing 15-min time trial. In double-blinded fashion, subjects ingested either four Q-chews or placebo chews (PL) 15 min prior to the treadmill runs. The four Q-chews provided 1000 mg quercetin, 120 mg epigallocatechin 3-gallate (EGCG), 400 mg isoquercetin, 400 mg eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), 1000 mg vitamin C, and 40 mg niacinamide. Subjects provided blood samples 30 min before, immediately following and 1-h post-exercise, and were analyzed for plasma quercetin concentration, total blood leukocytes (WBC), and nine inflammatory cytokines (IL-6, TNFα, GM-CSF, IFNγ, IL-1B, IL-2, IL-8, IL-10, IL-12p70) using an electrochemiluminescence based solid-phase sandwich immunoassay (Meso Scale Discovery, Gaithersburg, MD, USA). RESULTS: Plasma quercetin was elevated from 80.0±26.0 μg/L (pre-exercise) to 6,337±414 (post-exercise) and 4,324±310 μg/L (1-h post-exercise) after ingestion of Q-chews compared to no change in PL (interaction effect, P<0.001). No difference was measured between Q-chew and PL conditions in the distance run during the 15-min time trial (3.08±0.11 and 3.13±0.11 km, respectively, P=0.370). Exercise caused significant increases in WBCs, GM-CSF, IL-10, IL-1B, IL-2, IL-6, IL-8, and TNFα, but no differences in the pattern of change were measured between Q-chew and PL trials. CONCLUSIONS: Acute ingestion of Q-chews 15 min before heavy exertion caused a strong increase in plasma quercetin levels but did not counter post-exercise inflammation relative to placebo. These data are in contrast to the anti-inflammatory effect measured with this same quercetin-based supplement when consumed for two weeks prior to a 3-day period of intensified exercise (Med Sci Sports Exerc. 2009;41:1467-75). Taken together, these data imply that a prolonged Q-chew supplementation period is needed before anti-inflammatory effects can be achieved.

A 12-week supplementation with quercetin does not affect natural killer cell activity, granulocyte oxidative burst activity or granulocyte phagocytosis in female human subjects

Quercetin, a flavonoid found in fruits and vegetables, is a strong antioxidant with anti-inflammatory, antimicrobial and immune-modulating properties. The purpose of the present study was to investigate the effects of long-term quercetin supplementation on innate immune function and inflammation in human subjects. Female subjects (n 120; aged 30-79 years) were recruited from the community and randomised to one of three groups, with supplements administered using double-blinded procedures: 500 mg quercetin/d (n 38), 1000 mg quercetin/d (n 40) or placebo (n 42). Subjects ingested two soft chew supplements twice daily during the 12-week study period. Fasting blood samples were obtained pre- and post-study and were analysed for plasma quercetin, IL-6, TNF-alpha and leucocyte subset cell counts. Natural killer cell activity (NKCA) and lymphocyte subsets were assessed in a subset of seventy-four subjects. Granulocyte oxidative burst activity (GOBA) and phagocytosis were assessed in sixty-four subjects. Eighteen subjects had overlapping data. Quercetin supplementation at two doses compared with placebo increased plasma quercetin (interaction effect; P < 0.001) but had no significant influence on blood leucocyte subsets, plasma IL-6 or TNF-alpha concentration, NKCA, GOBA or phagocytosis. NKCA was inversely correlated with BMI (r - 0.25; P = 0.035) and body fat percentage (r - 0.38; P = 0.001), and positively correlated with self-reported physical fitness level (r 0.24; P = 0.032). In summary, results from the present double-blinded, placebo-controlled, randomised trial indicated that quercetin supplementation at 500 and 1000 mg/d for 12 weeks significantly increased plasma quercetin levels but had no influence on measures of innate immune function or inflammation in community-dwelling adult females.

In vivo effects of quercetin on innate immune function

Quercetin, a flavonoid found in fruits and vegetables, is an antioxidant with anti‐inflammatory, antimicrobial, and immune‐modulating properties. The purpose of this study was to investigate the effects of quercetin supplementation on innate immune function and inflammation in humans. Female subjects (N=120, ages 30–79 y) were randomized to one of three groups, with supplements administered for 12 wk using double‐blinded procedures: Q‐500 (500 mg/d quercetin, N=38), Q‐1000 (1000 mg/d quercetin, N=40), or placebo (N=42). Fasting blood samples were obtained pre‐ and post‐study and were analyzed for plasma quercetin, IL‐6, TNF‐α, and leukocyte subsets. Natural killer cell activity (NKCA) and lymphocyte subsets were assessed on 74 subjects. Granulocyte oxidative burst activity (GOBA) and phagocytosis were assessed on 64 subjects. Quercetin supplementation at two doses compared to placebo increased plasma quercetin (P&lt;0.001) but had no significant influence on leukocyte subsets, IL‐6, TNF‐α, NKCA, GOBA, or phagocytosis. In summary, results from this double‐blinded, placebo‐controlled, randomized trial indicated that quercetin supplementation at 500 and 1000 mg/d for 12 wk increased plasma quercetin levels but had no influence on measures of innate immune function or inflammation in healthy adult females. This work was supported by grants from Coca‐Cola and Quercegen Pharma.

Human antioxidant status is not altered by quercetin supplementation

The purpose of this study was to measure the influence of ingesting quercetin for 12 weeks at two doses relative to placebo on plasma measures for oxidative stress and antioxidant capacity in a large community group of male (40%) and female (60% female) subjects (N=1,002) varying widely in age (18 to 85 years) and body mass index (BMI) (16.7 to 52.7 kg/m2). Subjects were randomized to one of three groups, with supplements administered using double blinded procedures: Q‐500 (500 mg quercetin/day), Q‐1000 (1000 mg quercetin/day), or placebo (PL). Fasting blood samples were obtained pre‐ and post‐study. Plasma quercetin in Q‐500 and Q‐1000 increased significantly above PL, and monthly measures on a subset of subjects found that the increase peaked during the first month and was maintained for 12‐weeks. Plasma F2‐isoprostanes, oxidized low density lipoprotein (oxLDL), reduced glutathione (GSH), ferric reducing ability of plasma (FRAP), and oxygen radical absorbance capacity (ORAC) did not differ between supplementation groups, even after adjustment for gender, age, BMI, and disease status. In summary, quercetin supplementation, 500 mg or 1000 mg/day, for 12 weeks significantly increased plasma quercetin levels in a dose‐responsive manner, but did not influence several measures of oxidative stress and antioxidant capacity.Supported by grants from Coca‐Cola and Quercegen Pharma.

Quercetin supplementation does not alter antioxidant status in humans

This study measured the influence of ingesting quercetin on plasma measures for oxidative stress and antioxidant capacity. Male and female subjects (n = 1002) varying in age (18–85 years) and body mass index (BMI) (16.7–52.7 kg/m2) were studied. Subjects were randomized to one of three groups using double-blinded methods: placebo, 500 mg or 1000 mg quercetin/day with 125 mg or 250 mg vitamin C/day, respectively. Pre- and post-study fasting blood samples show that plasma quercetin increased in a dose-responsive manner. The pattern of change in plasma F2-isoprostanes, oxidized low density lipoprotein, reduced glutathione, ferric reducing ability of plasma (FRAP) and oxygen radical absorbance capacity (ORAC) did not differ between supplementation groups or after adjustment for gender, age, BMI and disease status. In summary, quercetin supplementation over 12 weeks in doses of 500 mg or 1000 mg/day significantly increased plasma quercetin levels, but had no influence on several measures of oxidative stress and antioxidant capacity.

Effects of quercetin on skeletal muscle mitochondrial biogenesis and performance in untrained males

We determined the influence of 2‐weeks quercetin supplementation (1000 mg/day) compared to placebo on exercise performance and markers of skeletal muscle mitochondrial biogenesis in 26 untrained, physically inactive, young adult males. Utilizing a randomized, crossover design with a 2‐week washout period, subjects provided blood and muscle biopsy samples pre‐ and post‐supplementation periods, and were given 12‐minute time trials on 15% graded treadmills following 60‐min moderate exercise pre‐loads at 60% VO2max. Plasma quercetin levels rose significantly during the two‐week quercetin compared to placebo supplementation period. During the 12‐minute trial (15% treadmill grade, self‐selected speed), the net change in distance achieved was significantly greater with quercetin compared to placebo (29.5±11.5 vs. ‐11.9±16.0 m, respectively, P=0.038). Skeletal muscle mRNA expression tended to increase during supplementation with quercetin compared to placebo for SIRT‐1 (P‐value=0.152), PGC‐1α (P=0.192), cytochrome c oxidase (P=0.081), and citrate synthase (P=0.166). In summary, 1000 mg/d quercetin supplementation for 2 weeks by untrained males was associated with an improvement in 12‐minute treadmill time trial performance and 16% to 25% increases above placebo levels for mRNA expression for four genes related to mitochondrial biogenesis.Supported by a Grant from Quercegen Pharma

Effect of apoE genotype and dietary quercetin on blood lipids and TNF-α levels in apoE3 and apoE4 targeted gene replacement mice

The aim of this study was to determine the effect of dietary quercetin supplementation on blood lipids and TNF-alpha levels according to the apoE genotype in apoE3 and apoE4 targeted gene replacement mice. In a two-factorial design female apoE3 and apoE4 mice were fed semi-synthetic diets without (controls) and with quercetin (2 mg/g diet) for 6 weeks. Feeding the quercetin-supplemented diets significantly increased plasma levels of quercetin and isorhamnetin both in apoE3 and apoE4 mice. There was no significant effect of apoE genotype on plasma quercetin levels. ApoE3 and apoE4 transgenic mice exhibited similar plasma levels of apoE and cholesterol which were not significantly affected by dietary quercetin supplementation. In mice receiving the basal diet without quercetin supplementation, levels of TNF-alpha in whole blood stimulated ex vivo with lipopolysaccharide were higher in apoE3 as compared to apoE4 transgenic mice. Dietary quercetin significantly lowered levels of TNF-alpha by 44 % in apoE3 mice relative to apoE3 mice receiving the unsupplemented diets. In apoE4 mice a moderate (20 %) but not significant decrease in TNF-alpha levels in response to the quercetin supplementation was evident. Following quercetin supplementation TNF-alpha levels were similar between apoE3 and apoE4 transgenic mice. Current findings indicate that apoE3 mice are more responsive to the TNF-alpha lowering properties of dietary quercetin supplementation as compared to apoE4 animals.

Quercetin Ingestion Does Not Alter Cytokine Changes in Athletes Competing in the Western States Endurance Run

The purpose of this study was to measure the influence of quercetin on plasma cytokines, leukocyte cytokine mRNA, and related variables in ultramarathoners competing in the 160-km Western States Endurance Run (WSER). Sixty-three runners were randomized to quercetin and placebo groups and under double-blinded methods ingested 1000 mg/day quercetin for 3 weeks before the WSER. Thirty-nine of the 63 subjects (n = 18 for quercetin, n = 21 for placebo) finished the race and provided blood samples the morning before the race and 15-30 min postrace. Significant prerace to postrace WSER increases were measured for nine proinflammatory and anti-inflammatory plasma cytokines, cortisol (quercetin = 94%, placebo = 96%), serum C-reactive protein (CRP) (mean +/- SE absolute increase, quercetin = 31.8 +/- 4.2, placebo = 38.2 +/- 5.0 mg/L), and creatine kinase (CK) (quercetin = 21,575 +/- 3,977, placebo = 19,455 +/- 3,969 U/L), with no significant group differences. Interleukin-6 (IL-6) mRNA did not change post-WSER, with a significant decrease measured for leukocyte IL-8 mRNA (0.21 +/- 0.03-fold and 0.25 +/- 0.04-fold change from rest, quercetin and placebo, respectively) and significant increases for IL-1Ra mRNA (1.43 +/- 0.18-fold and 1.40 +/- 0.16-fold change, quercetin and placebo, respectively) and IL-10 mRNA (12.9 +/- 3.9-fold and 17.2 +/- 6.1-fold change, quercetin and placebo, respectively), with no significant differences between groups. In conclusion, quercetin ingestion (1 g/day) by ultramarathon athletes for 3 weeks before a competitive 160-km race significantly increased plasma quercetin levels but failed to attenuate muscle damage, inflammation, increases in plasma cytokine and hormone levels, and alterations in leukocyte cytokine mRNA expression.

Quercetin's influence on exercise-induced changes in plasma cytokines and muscle and leukocyte cytokine mRNA

Trained male cyclists (n = 40) ingested quercetin (Q; n = 20) (1,000 mg/day) or placebo (P; n = 20) supplements under randomized, double-blinded methods for 3 wk before and during a 3-day period in which subjects cycled for 3 h/day at approximately 57% maximal work rate. Blood samples were collected before and after each exercise session and assayed for plasma IL-6, IL-10, IL-1ra, IL-8, TNF-alpha, and monocyte chemoattractant protein 1, and leukocyte IL-10, IL-8, and IL-1ra mRNA. Muscle biopsies were obtained before and after the first and third exercise sessions and assayed for NF-kappaB and cyclooxygenase-2 (COX-2), IL-6, IL-8, IL-1beta, and TNF-alpha mRNA. Postexercise increases in plasma cytokines did not differ between groups, but the pattern of change over the 3-day exercise period tended to be lower in Q vs. P for IL-8 and TNF-alpha (P = 0.094 for both). mRNA increased significantly postexercise for each cytokine measured in blood leukocyte and muscle samples. Leukocyte IL-8 and IL-10 mRNA were significantly reduced in Q vs. P (interaction effects, P = 0.019 and 0.012, respectively) with no other leukocyte or muscle mRNA group differences. Muscle NF-kappaB did not increase postexercise and did not differ between Q and P. Muscle COX-2 mRNA increased significantly postexercise but did not differ between Q and P. In summary, 1 g/day quercetin supplementation by trained cyclists over a 24-day period diminished postexercise expression of leukocyte IL-8 and IL-10 mRNA, indicating that elevated plasma quercetin levels exerted some effects within the blood compartment. Quercetin did not, however, influence any of the muscle measures, including NF-kappaB content, cytokine mRNA, or COX-2 mRNA expression across a 3-day intensified exercise period.

Bioavailability of Quercetin From Berries and the Diet

: Berries are a rich source of various polyphenols, including the flavonoid quercetin. In this article, the results of three intervention studies investigating the bioavailability of quercetin from berries are reviewed. In the first study, we investigated the short-term kinetics of quercetin after consumption of black currant juice and showed that quercetin is rapidly absorbed from it. In the second study, we showed that plasma quercetin levels increase up to 50% in subjects consuming 100 g/day of bilberries, black currants, and lingonberries as a part of their normal diets for 2 mo. In the third study, healthy subjects consumed a diet high or low in vegetables, berries, and other fruit for 6 wk. Quercetin concentrations nearly doubled in the high-vegetable, -berry, and -other fruit group and decreased by 30% in subjects consuming less of these foods than normally. The results showed that plasma quercetin is bioavailable from a diet containing berries and indicate that it may be a good biomarker of fruit and vegetable intake in general.